阅读说明：本技术 一种用于治疗和预防糖尿病足的药物组合物 (A pharmaceutical composition for treating and preventing diabetic foot ) 是由 张娟子 王兆伟 于 2020-06-09 设计创作，主要内容包括：本发明涉及医药技术领域,具体涉及一种用于治疗和预防糖尿病足的药物组合物,所述组合物包括N-(5-(4-甲基-1H-咪唑-1-取代)-3-(三氟甲基)-苯基)-4-甲基-3-(4-吡啶-3-取代-噻唑-2-取代氨基)-苯甲酰胺和原儿茶酸。实验结果表明该组合物可以明显加快糖尿病足伤口愈合,并具有显著抑制耐药铜绿假单胞菌的效果,不仅可用于加快糖尿病足伤口愈合,还有助于糖尿病足耐药菌感染的治疗,有利于避免抗生素耐药问题。(The invention relates to the technical field of medicines, and particularly relates to a pharmaceutical composition for treating and preventing diabetic foot, which comprises N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide and protocatechuic acid. The experimental result shows that the composition can obviously accelerate the wound healing of the diabetic foot, has the effect of obviously inhibiting drug-resistant pseudomonas aeruginosa, can be used for accelerating the wound healing of the diabetic foot, is beneficial to the treatment of drug-resistant bacteria infection of the diabetic foot, and is beneficial to avoiding the problem of antibiotic resistance.)

1. A pharmaceutical composition for the treatment and prevention of diabetic foot, comprising N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide.

2. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition further comprises protocatechuic acid.

3. The pharmaceutical composition according to claim 2, wherein the weight ratio of N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide to protocatechuic acid in the composition is 1.5-4.7: 1.

4. The pharmaceutical composition according to claim 3, wherein the weight ratio of N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide to protocatechuic acid in the composition is 2.3: 1.

5. The pharmaceutical composition according to claims 1 to 4, wherein the pharmaceutical composition is capable of resisting diabetic foot-resistant bacterial infections.

6. The pharmaceutical composition of claim 5, wherein the drug-resistant bacteria is drug-resistant Pseudomonas aeruginosa.

7. The pharmaceutical composition according to claims 1 to 6, wherein the composition is an oral preparation or an external preparation.

Use of N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide in the preparation of a medicament for the treatment and prevention of diabetic foot.

Use of N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide in the preparation of a medicament for treating drug-resistant bacterial infection of diabetic foot.

Technical Field

The invention relates to the technical field of medicines, in particular to a pharmaceutical composition for treating and preventing diabetic foot.

Background

Diabetic foot is one of the most serious chronic complications of diabetes, and is one of the main causes of disability of diabetic patients, and the death rate caused by amputation is quite high, wherein the diabetic foot is caused by arteriosclerosis obliterans in the middle and small lower limbs, thrombosis, acral ischemia, thickening of microvascular basement membrane, stenosis of lumen, skin neurotrophic disorder caused by skin neurotrophic disorder and diabetes mellitus cause peripheral nerve segmental demyelination, nerve cell and axonal degeneration, nerve membrane damage, and sensory and motor nerve function reduction. At present, the metabolic disorders of blood fat and blood sugar are considered to be closely related to the occurrence of the metabolic disorders. The lower limb protection function of the diabetic patient is reduced, the ischemia and resistance of local tissues are reduced, the infection can be caused by tiny wounds to form ulcer, the growth of bacteria in the tissues with high sugar content is suitable, the infection rate is increased, the infected wounds are difficult to heal, the course of disease is prolonged, and great pain and economic burden are brought to the patient and families. Therefore, the development of an effective pharmaceutical composition for preventing and treating diabetic foot has important practical significance.

With the wide application of antibiotics, the rate of formation of microbial resistance increases proportionally to the ability of antibiotics to sterilize, so that the continued use of antibiotics accelerates the formation of multi-resistant strains. The diabetic foot causes the damage of skin soft tissues and the invasion of exogenous bacteria, thereby improving the bacterial infection of the diabetic foot, particularly improving the treatment difficulty of drug-resistant bacterial infection of the diabetic foot, and seriously causing local soft tissue infection and even the formation of osteomyelitis. Currently, antibiotic resistance has become a serious public health problem worldwide.

The pyridine compounds and the derivatives thereof have antibacterial and antiviral activities, and the novel diabetes foot medicament is developed by modifying the existing pyridine type structure, so that the pyridine compounds and the derivatives thereof have wide prospects. N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide is a pyridylthiazole ammonium compound, the structure of which is shown in the specification, and no literature report related to the diabetic foot exists at present.

Disclosure of Invention

Aiming at the defects in the prior art, one of the purposes of the invention is to provide a pharmaceutical composition for treating and preventing diabetic foot, the pharmaceutical composition can obviously accelerate wound healing of diabetic foot, has the effect of obviously inhibiting drug-resistant pseudomonas aeruginosa, can be used for accelerating wound healing of diabetic foot, is also beneficial to treatment of drug-resistant bacterial infection of diabetic foot, and is beneficial to avoiding the problem of antibiotic resistance.

The above object of the present invention is achieved by the following technical solutions:

a pharmaceutical composition for the treatment and prevention of diabetic foot comprising N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide.

Preferably, the pharmaceutical composition further comprises protocatechuic acid.

Preferably, the weight part ratio of the N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide to the protocatechuic acid in the composition is 1.5-4.7: 1.

Preferably, the weight parts ratio of N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide to protocatechuic acid in the composition is 2.3: 1.

Preferably, the pharmaceutical composition is capable of resisting diabetic foot-resistant bacterial infection, and the resistant bacteria is drug-resistant pseudomonas aeruginosa.

Preferably, the composition is an oral preparation or an injection.

It is another object of the present invention to provide the use of N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide in the manufacture of a medicament for the treatment and prevention of diabetic foot.

Furthermore, the invention also provides application of the 2-methoxy-9 acridine mercaptotetrazole in preparing a medicine for treating diabetic foot drug-resistant bacteria infection.

Compared with the prior art, the invention has the following beneficial technical effects:

1) the invention firstly explains that the N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide has definite therapeutic action on diabetic feet, has good hypoglycemic effect, provides a good lead compound for developing novel diabetic foot medicaments, and has wide application prospect.

2) The N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide has a remarkable inhibiting effect on the infection of drug-resistant bacteria of diabetic feet, and remarkably shortens the healing time of ulcer after the infection of the drug-resistant bacteria of diabetic feet, and simultaneously, the N- (5- (4-methyl-1H-imidazole-1-substituted) -3- (trifluoromethyl) -phenyl) -4-methyl-3- (4-pyridine-3-substituted-thiazole-2-substituted amino) -benzamide and the protocatechu in the pharmaceutical composition are The acids cooperate with each other, thereby providing a non-antibiotic drug-resistant bacteria medicament, in particular a non-antibiotic drug-resistant bacteria infection medicament for treating diabetic foot, which is helpful for avoiding the problem of antibiotic resistance.

Detailed Description

The present invention will be described in further detail below.